Neuroserpin Polymers Activate NF-κB by a Calcium Signaling Pathway That Is Independent of the Unfolded Protein Response
Neuroserpin Polymers Activate NF-κB by a Calcium Signaling Pathway That Is Independent of the Unfolded Protein Response
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DOI：
10.1074/jbc.m109.010744
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发表时间：
2009-07-03
影响因子：
4.8
通讯作者：
Lomas, David A.
中科院分区：
文献类型：
--
作者：
Davies, Mark J.;Miranda, Elena;Lomas, David A.
常染色体显性痴呆家族性脑病伴神经丝氨酸包涵体的特点是突变的神经丝氨酸在神经元内质网内有序聚合物的积累。我们在这里表明，细胞内神经丝氨酸蛋白聚合物通过一种独立于典型未折叠蛋白反应的IRE1、ATF6和PERK分支的途径激活NF-kappa B，但依赖于细胞内钙。这一途径为细胞感知内质网内突变蛇蛋白折叠结构的积累并作出反应提供了一种机制。我们的研究结果为内质网过载反应独立于未折叠蛋白反应提供了强有力的支持。
The autosomal dominant dementia familial encephalopathy with neuroserpin inclusion bodies is characterized by the accumulation of ordered polymers of mutant neuroserpin within the endoplasmic reticulum of neurones. We show here that intracellular neuroserpin polymers activate NF-kappa B by a pathway that is independent of the IRE1, ATF6, and PERK limbs of the canonical unfolded protein response but is dependent on intracellular calcium. This pathway provides a mechanism for cells to sense and react to the accumulation of folded structures of mutant serpins within the endoplasmic reticulum. Our results provide strong support for the endoplasmic reticulum overload response being independent of the unfolded protein response.